tbuckley/cabot-search huggingface dataset:
Quality initiative (QI) to improve molecular testing in newly diagnosed (ND) stage 4 non-small cell lung cancer (NSCLC-4): An Integra Connect (IC) database study.
Authors: Mike Gart, Rushir J. Choksi, Daniel P. Petro, Jeffrey A. Scott, Prateesh Varughese, Matt Stockton, Robert E. Smith
Journal: Journal of Clinical Oncology (2022)

e13507 Background: In August 2019 IC partnered with University of Pittsburg Medical Center (UPMC) on a QI aimed at improving outcomes in stages 3 and 4 NSCLC. This report details the findings, interventions, and results in the stage 4 cohort to date. Guidelines advocate broad molecular profiling and completion of biomarker testing prior to initiation of initial therapy (KF Mileham,2022). However, real world data has shown a high rate of treatment initiation without biomarker testing due to low rate of testing and, if tested, treatment prior to results reporting (H West,2021; J Nicholas, 2021) in this disease state having a 5-year survival of only 7% (N Howlander). Based on analysis of the US Oncology Network it was found that only 46% of patients (pts) with metastatic NSCLC received testing for PD-L1, EGFR, ALK, ROS1, and BRAF-V600E (J Nicholas, 2021). Methods: By querying the UPMC and IC databases, 847 patients (pts) with ND NSCLC-4 were identified who received an initial line of therapy, excluding squamous carcinoma pts unless documented never-smokers, during 1/1/2017- 12/31/2021. Date of EGFR test ordered, date of test result report to electronic health record, and date of treatment initiation were captured. Also included were test orders for the NCCN recommended biomarker panel of PD-L1, ALK, ROS1, BRAF, RET, MET, and NTRK. The data were evaluated in three time periods for the QI: Phase 1 of 1339 days (1/1/2017-8/31/2020) for baseline, Phase 2 of 122 days (9/1/2020-12/31/20) post physician leadership intervention, and Phase 3 of 272 days (1/1/2021-9/30/2021) performance measurement period. Baseline and on-going measurement of testing metrics was performed with physician leadership intervention for identified gaps in care. Additionally, surveys were implemented to assess caregiver perceptions. The use of chart curation and software-based monitoring tools powered by IC enabled providers to understand current levels of testing and track performance over time. Results: Median age was 68 (range 36 - 89) and 49% male. As shown in Data Table, EGFR testing at baseline was 94% and increased to 96%. Testing of the entire biomarker panel noted above increased from 52% baseline to 76% at this point in Phase 3. While only 72% had treatment initiated after EGFR result at baseline, this improved to 88% during Phase 3. Conclusions: This QI led to improvement in rates of broad biomarker testing and initiation of treatment only after results were made available in this NSCLC-4 population. While this initiative was not designed to evaluate outcomes, one would expect outcome improvement over baseline with higher guideline adherence.[Table: see text]
Functional activity of peripheral blood mononuclear cells in patients with non-Hodgkin's lymphomas receiving treatment after COVID-19 disease.
Authors: Aleksandr B. Sagakyants, Irina B. Lysenko, Oksana G. Shulgina, Inna A. Kamaeva, Ekaterina I. Zolotareva, Inna A. Novikova, Liubov Yu Vladimirova, Oleg I. Kit, Elena A. Dzhenkova, Elena Yu Zlatnik, Viktoria V. Dmitrieva, Nadezhda V. Nikolaeva
Journal: Journal of Clinical Oncology (2022)

e19564 Background: Patients with non-Hodgkin's lymphomas (NHL) develop abnormalities in the structural and functional organization of the immune system leading to immune deficiency. Chemotherapy (CT) in patients after SARS-CoV infection is associated with a more severe disease course affecting the treatment results. The cytokine-producing activity (CPA) of blood cells is poorly studied, while it determines the effectiveness of antitumor and anti-infective functions of the immune system. The purpose of this study was to evaluate CPA of peripheral blood mononuclear cells in patients receiving treatment for NHL after COVID-19. Methods: The study included 8 patients with large B-cell NHL with PCR-confirmed COVID-19 infection in past medical history. All patients received from 3 to 4 chemotherapy cycles. K2EDTA blood samples obtained before and after 3-4 CT cycles were divided into 2 parts after dilution with a sterile nutrient medium solution: part 1, to assess spontaneous CPA; part 2, with addition of a sterile mitogen (phytohemagglutinin 4 μg, concanavalin A 4 μg, and lipopolysaccharide 2 μg) to assess stimulated CPA. The samples were incubated for 24 hours at 37 0 C, and the levels of IL-1β, IL-6, IL-8, IL-10, IL-18, IL-4, IL-2, TNF- α, INF-ɣ, INF-α were determined in the obtained plasma. The stimulation coefficient (SC) was calculated as the ratio of stimulated CPA to spontaneous CPA. Results: 3-4 CT cycles in patients after COVID-19 was accompanied by an elevation of spontaneous CPA of the blood cells IL-6, INF-ɣ, TNF-α, IL-8, compared to the initial levels, by 678%, 127%, 64% and 57%, respectively. The ability of cells to spontaneous production of IL-10 and INF-α decreased by 30% and 100%. The mitogen-induced CPA of mononuclear cells in relation to IL-10, IL-6, IL-2, IL-1β and INF-α increased by 300%, 130%, 92%, 52% and 52%, respectively. Stimulated CPA in relation to INF-ɣ decreased by 21% compared to initial levels. As a result of the revealed CPA changes, SC in NHL patients after COVID-19 receiving CT increased, compared to the initial levels, by 465%, 92% and 48% respectively for IL-10, IL-2, IL-1β, as well as the appearing ability to INF-α production. SC for IL-6, INF-ɣ, TNF-α, and IL-8 decreased by 70%, 66%, 33% and 27% respectively. Conclusions: Certain features of spontaneous and mitogen-activated CPA of blood mononuclear cells were revealed in NHL patients after COVID-19, indicating a change in the functional activity of immune cells which could affect the development of the disease and the effectiveness of the therapy. The data obtained require additional studies and can be used to assess the condition of patients, as well as to predict the therapy efficacy.
Treatment pattern and outcomes in patients with uncommon or compound EGFR mutations in India: CRSF 2020-03 study.
Authors: Manuprasad Avaronnan, Rushabh Kothari, Avinash Talele, Vikas Talreja, Gautam Goyal, Nirmal Vivek Raut, Ashay Karpe
Journal: Journal of Clinical Oncology (2022)

e21034 Background: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) resulted in significant improvement in the outcomes of patients with activating EGFR mutations. But the ideal treatment of patients harboring uncommon, or compound mutations is not well defined. This multicentric audit was conducted to study the distribution, treatment pattern, and outcomes of patients with uncommon or compound EGFR mutations. Methods: This was a multicentric retrospective study that included patients with uncommon (mutations other than Exon 19 deletions and Exon 21 L858R) or compound (double or complex) mutations treated during the period of 2017-2020. Statistical analysis was done using SPSS version 20.0. Descriptive statistics were used wherever appropriate. Kaplan Meier Aanlaysis was performed for estimation of PFS and OS. Results: Total 99 patients with uncommon or compound mutations were included in the study. The median age was 55 years (25-82 years). Majority were males (n=65,67%) and 47 (47%) were smokers. Sixty-seven patients (68 %) had a single uncommon mutation and the remaining 32 (32%) had compound mutations. Most common mutations were exon 20 insertion (n=34, 35%) and T790M (N=16,16%). Other frequent mutations observed were exon 18 G719X (n=7,7%) and exon 21 L861Q (n=3,3%). Twenty-three patients (n=23,23%) were eligible only for best supportive care. Thirty-two patients (32%) received first-generation TKI, 30 patients (30%) received palliative chemotherapy and 11 patients (11 %) received Osimertinib. Gefitinib with chemotherapy was used in 2 patients and combination of Gefitinib with Afatinib was used in one patient. Overall response rate and clinical benefit rate with first line treatment was 23% and 35% respectively. Response could not be assessed in 14 patients. Median PFS was 5 months (95% CI 3.4-6.9) and median OS was 8.3 months (95% CI 3.3- 13). In patients who received any form of systemic treatment, median PFS was 6.2 months (95% CI- 3.3-9.1) and OS was 11 months (95% CI -8.9-13.9). Conclusions: The most frequent uncommon mutations in India are exon 20 insertion followed by compound mutations and exon 20 T790M mutation. Outcomes of patients with these rare mutations are dismal in the real world setting with the available treatment options.
Characterizing genitourinary exam disruptions in women presenting to a sexual health after cancer program.
Authors: Sanjana Satish, Fay Pon, Carmen Julia Calfa, Alejandra T. Perez, Kristin E. Rojas
Journal: Journal of Clinical Oncology (2022)

e24048 Background: While treatment-related sexual health sequelae are documented using validated patient-reported outcome measures, the anatomic changes associated with cancer treatment are not well described, which may lead to an underestimation of the severity of these symptoms. To fill this knowledge gap and improve the management of these anatomic disruptions, we sought to objectively report the genitourinary findings of women presenting to a sexual health after cancer program over one year. Methods: At their first visit, patients undergo a thorough history and physical with a focus on the genitourinary exam. Patient demographics, primary symptoms, and treatment history were retrospectively collected and correlated to vaginal assessment scale (VAS) scores of female cancer patients presenting to the MUSIC (Menopause, Urogenital, Sexual Health and Intimacy Clinic) Program at an NCI-designated cancer center. Results: Between 2020-2021, 104 female cis-gender women with a median age of 46 (range 19-75) at diagnosis were seen. 56% identified as Hispanic/Latinx. Mean age was 47 (19-75), and most were treated for breast (80%) or gynecologic (10%) cancer. Primary complaints included vaginal dryness (53%), painful sex (45%), low desire (36%), hot flashes (22%), problems with orgasm (5%), urinary symptoms (10%), chronic pelvic pain (4%), or a need for complex contraceptive counseling (1%). Of those where a VAS was performed (n = 89), patients were found to have mild or moderate/severe loss of rugae (78%), loss of elasticity (84%), loss of vascularity (86%), and/or dryness (88%). Alarmingly, almost half were found to have some element of vaginal stenosis on exam, either vaginal scarring/adhesions (6%), foreshortened vagina (13%), or a narrowed introitus (47%) (Table). Conclusions: In an initial consult of women seeking care for sexual health after cancer treatment, the most common concerns were vaginal dryness, painful sex, and low desire. Despite only approximately half reporting either dryness or painful sex, most were found to have genitourinary disruptions in anatomy at presentation, including vaginal stenosis. The presence of vaginal stenosis in sexual health survivors who did not undergo pelvic radiation deserves future study as these findings often present as a complete inability to have penetrative intercourse.[Table: see text]
Clinical outcomes associated with azacitidine (AZA) monotherapy for treatment-naïve, higher-risk myelodysplastic syndrome (HR-MDS): A systematic literature review and meta-analysis.
Authors: Ken Hasegawa, Andrew H. Wei, Guillermo Garcia-Manero, Naval Guastad Daver, Nishanthan Rajakumaraswamy, Shahed Iqbal, Rebecca J. Chan, Hao Hu, Preston Tse, Jiajun Yan, Michael J. Zoratti, Feng Xie, David Andrew Sallman
Journal: Journal of Clinical Oncology (2022)

e19062 Background: AZA is a standard of care for patients who have HR-MDS. Given the limited availability of large datasets describing outcomes in the current treatment paradigm of HR-MDS, this analysis aimed to aggregate clinical outcomes associated with AZA monotherapy for treatment-naïve HR-MDS. Methods: CENTRAL, EMBASE, and MEDLINE were searched to identify interventional, prospective, and retrospective observational studies in treatment-naïve HR-MDS (defined as intermediate-2 or high risk by IPSS or intermediate to very high risk by IPSS-R) using AZA monotherapy. Inclusion of observational studies was limited to those with n &gt;20 in the AZA arm. Responses according to IWG 2000 or IWG 2006 including complete remission (CR) rate, overall response rate (ORR; defined as CR, marrow CR [mCR], partial response, and hematologic improvement), overall survival (OS), duration of response (DOR), and time to response (TTR) were extracted. Response rates were synthesized using random-effects models; median of medians was used for OS, DOR, and TTR. Results: Of 3250 abstracts identified, 34 publications describing 16 studies met inclusion criteria: 5 randomized controlled trials (RCTs), 3 prospective studies, and 8 retrospective studies. None of the response endpoints were reported in all studies (see Table). The pooled ORR ranged from 44% to 55% across RCTs, prospective, and retrospective studies. The pooled CR rates, reported in 2 RCTs (n=55), 1 prospective study (n=27), and 3 retrospective studies (n=509), were 14%, 11%, and 16%, respectively. The pooled CR rate across all studies (n=591) was 16% (95% CI: 13%, 19%). Pooled median OS (mOS) was 16.7 months (mo) in the 3 RCTs (n=161), 16.5 mo in a single prospective study (n=34), and 14.4 mo in the 5 retrospective studies (n=1472). Pooled mOS across all studies (n=1667) was 16.4 mo (95% CI: 12.0, 17.3). The pooled median DOR was 10.1 mo (95% CI: 9.1, 11.0), and the median TTR was 4.6 mo (95% CI: 3.0, 9.0). Conclusions: These findings provide evidence that benefit from AZA monotherapy in treatment-naïve HR-MDS patients is limited. Opportunity exists for novel therapies to increase response rates, improve the duration of responses, and prolong survival. [Table: see text]
<i>TP53</i> gain-of-function mutations and impact on CDKN2A mutation on prognosis of pancreatic ductal adenocarcinoma.
Authors: Minggui Pan, Chen Jiang, Zheyang Zhang, Ninah Achacoso, Pamela Tse, Aleyda Solorzano, Elaine Chung, Tilak Kumar Sundaresan, Jennifer Marie Suga, Jianliang Huang, Sachdev P. Thomas, Laurel A. Habel
Journal: Journal of Clinical Oncology (2022)

e16294 Background: Developmentally pancreas head derives from ventral bud while pancreas neck, body and tail derive from dorsal bud. Pancreatic ductal adenocarcinoma (PDAC) frequently harbors multiple mutations including KRAS, TP53, CDKN2A, and others. It is unknown how TP53 gain-of-function (GOF) and non-gain-of-function (non-GOF) mutations affect the prognosis. Methods: We retrospectively examined a cohort of 741 Kaiser Permanente (KP) patients with locally advanced/metastatic PDAC who had NGS performed to determine the association of KRAS (mutKRAS), TP53 (mutp53) and CDKN2A (mutCDKN2A) mutations (individually and in combination) with overall survival (OS). We used Cox modeling to estimate hazard ratios (HR) adjusted for age, sex, ethnicity, performance status, Charlston Comorbidity Index, chemotherapy received, anatomic location and co-mutations. We also analyzed the TCGA PDAC dataset to examine the association of OS with these same mutations. Results: In the KP cohort, patient ages ranged from 36 to 94 years and approximately 50% were female. In 384 patients PDAC was on the head, and 357 patients had PDAC on a non-head location (neck, body, and tail). Those with head PDAC had modestly better OS compared to non-head PDAC (HR = 0.87), and this appeared to be driven by the subsets of patients with wtp53 (HR = 0.68), with wtKRAS (HR = .74) and with wtCDKN2A (HR = .78). Approximately 67.5% of patients had mutp53, 89.2% had mutKRAS and 44.8% had mutCDKN2A. Among all KP patients, OS was similar for patients with mutp53 vs. wtp53 (HR = 1.05); worse for patients with mutKRAS vs. wtKRAS (HR = 1.26), and worse for patients with mutCDKN2 vs. wtCDKN2A (HR = 1.51). Interestingly, among patients with a GOF mutp53, those with mutCDKN2A had substantially worse OS vs patients with wtCDKN2A (HR = 2.56, 95% CI 1.46-4.50). In contrast, among patients with a non-GOF mutp53, patients with mutCDKN2A had only moderately worse OS compared to patients with wtCDKN2A (HR = 1.37, 95% CI 1.06-1.79). Analysis of the TCGA PDAC dataset showed that the number of mutations (0, 1, 2, or 3, of p53, KRAS and CDKN2A) was associated with incrementally worse OS ( p &lt; .001). Conclusions: Better OS of head vs. non-head PDAC was primarily driven by patients with wtp53, wtKRAS, and wtCDKN2A. The adverse effect of mutCDKN2A on OS appears to be most pronounced in patients with GOF mutp53. Our TCGA analysis suggests interactions among TP53, KRAS and CDKN2A mutations in affecting PDAC survival.
Episodic future thinking: A behavioral intervention to promote weight loss in breast cancer survivors.
Authors: Jasmine S Sukumar, Jennifer Vaughn, Jeffrey Stein, Patrick Schnell, Preeti Khetarpal Sudheendra, Ashley Pariser, Margaret Elena Gatti-Mays, Nicole Olivia Williams, Mathew Amprayil Cherian, Daniel G. Stover, Robert Wesolowski, Bhuvaneswari Ramaswamy, Maryam B. Lustberg, Sagar D. Sardesai
Journal: Journal of Clinical Oncology (2022)

TPS12139 Background: Obesity at diagnosis is associated with an increase in breast cancer (BC) specific mortality. Behavioral interventions targeting obesity-related health choices offer a scalable approach to improve patient engagement in the community. Episodic Future Thinking (EFT) is a novel remotely delivered behavioral intervention which engages the science of prospection where participants mentally simulate positive, detailed, and personal events that can occur in the future. EFT targets a key behavioral economic measure – Delay Discounting (DD). As DD rate rises, an individual devalues future outcomes to a greater degree and has a higher bias for immediate gratification. EFT can decrease DD in obese patients, leading to improved diet quality and weight loss. However, valuation of the future may impact cancer survivors differently. Herein, we propose the first randomized Phase II trial evaluating adherence and changes in DD and body weight with 12-week remotely delivered EFT vs control in overweight or obese BC survivors. Methods: Eligible patients have a history of DCIS or stage 1 to 3 BC, BMI &gt; 25 kg/m 2 , have completed surgery, radiation, and chemotherapy, and are motivated to lose weight. They are randomized 1:1 to a 12-week EFT intervention or control (Episodic Recent Thinking; ERT). ERT is a validated control in which patients imagine events in the recent past. Randomization will be stratified by baseline DD rate. There is an optional 12 week follow up period where patients can continue to receive EFT or ERT cues. DD will be measured at baseline and every 4 weeks for 24 weeks. The primary endpoint is adherence, measured by percentage of thrice daily smartphone prompts participants open and attend to during the 12-week trial. Secondary endpoints are changes in body weight and DD rate at 12 and 24 weeks and change in PROs (PROMIS scales), insulin resistance (HOMA-IR), hs-CRP, and diet quality (HEI 2015) at 12 weeks from baseline. With 20 subjects per arm, the study has 80% power to detect deviation of 14 points from a target adherence rate of 80% using a 1 sample t-test. The primary endpoint is evaluable for all subjects, regardless of drop-out. Secondary endpoints will be evaluated using a linear mixed effects model. Hypothesis tests and confidence intervals will be two-sided at 5% significance/95% confidence level. Since trial activation in November 2021, 9 of the planned 46 patients are enrolled. Accrual is closely integrated with the dedicated Ohio State University Comprehensive Cancer Center Survivorship Program. This work is supported by the Alliance Cancer Control Program Pilot Award (5UG1CA189823-08). Clinical trial information: NCT05012176.
Female representation in oncology leadership in Africa: Analysis of trends in the African organization for cancer research and training in cancer (AORTIC).
Authors: Miriam Claire Mutebi, Naa Adorkor Aryeetey, Laura M. Carson, Haimanot Kasahun Alemu, Verna D. Vanderpuye, Nazik Hammad
Journal: Journal of Clinical Oncology (2022)

11052 Background: Board membership in oncology organizations and invitation to speak at major oncology conferences is an established indicator of gender disparities in oncology leadership. Recent studies note an upward trend in female board membership and female speakers at oncology conferences in European and American contexts. However, little is known about trends of female representation in board membership and at oncology conferences in Africa. AORTIC is the premier African cancer organization and hosts a biennial conference, during which its council members are elected for a two-year term. The conference hosts over 1000 participants and is highly regarded internationally. As the largest gathering of African oncologists, the conference presents a unique opportunity for insight into workforce disparities and trends. This study presents an analysis of female council membership and speaker participation at the 2015, 2017, 2019 and 2021 AORTIC conferences. Methods: AORTIC conference programmes and AORTIC elections for council membership in 2015, 2017, 2019 and 2021 were analyzed for gender representation. Speakers were divided into categories including keynote speakers, facilitators, session speakers, panelists, and oral abstract presenters. For each AORTIC session, data was collected on speaker name, gender, and affiliated country. Participants who presented multiple times were counted multiple times, as their role often varied between sessions. Personal data and country affiliation was determined through online biographies of speakers and/or visual confirmation of professional photographs. A simple descriptive analysis of the data and trends is presented here. Results: Since 2015, the proportion of female speakers and council members at AORTIC has increased. In 2015, females accounted for 44% of speakers, in contrast to 55% in 2021. In 2021, females made up over 50% of all speaker categories except keynote. The proportion of female council members also increased, from 42% in 2015 to 69% in 2021. Trends in geographic representation of speakers were also analyzed for gender, revealing an increase in female speakers residing in Africa. (Table) Conclusions: The proportion of female speakers and council members at Africa’s largest cancer conference has increased significantly since 2015. Female speaker participation was higher than in North America and Europe in 2017 and surpassed 50 % in 2021. In addition, female council membership in AORTIC has surpassed 50%, up to 69% in 2021. These trends suggest a rise in female leadership in cancer research and training on the continent, indicating that strengthening local platforms in LMIC may be associated with improved gender assimilation. [Table: see text]